Colchicine for Type 2 diabetes

Stratification factors

• Aspirin intake at time of randomization (yes/no)
• Eligibility to the aspirin arm (eligible vs not eligible)

Inclusion criteria

• {"criterion_text":"- Men and women aged 55 to 80 years\n- Type 2 diabetes treated as per national guidelines\n- No previous history of coronary artery disease-related clinical event\n- At least one of the following: a. Duration of diabetes of 5 years or more b. HbA1c ≥ 8.0% or more in the last 2 years c. Active cigarette smoking d. High hs-CRP (> 2.0 mg/L) e. High coronary calcium score (Agatston score >100) f. High TG-levels (≥1.7 mmol/L) despite lipid lowering therapy administered as per guidelines g. High LDL-C levels (≥3.5 mmol/L) or high non-HDL-C levels (≥4.2 mmol/L) despite lipid lowering therapy administered as per guidelines h. High Apo-B (≥1.05 g/L) i. Reduced HDL-C (<1.05 mmol/L in men, <1.3 mmol/L in women) j. Lp(a) >50 mg/dL k. Peripheral artery disease with stenosis ≥50% or prior revascularization l. Cerebrovascular disease with stenosis ≥50% or prior revascularization m. Diabetic retinopathy or diabetic neuropathy n. Mild or moderate proteinuria (dipstick analysis) or microalbuminuria\n- Women of childbearing potential must have a negative urine pregnancy test at screening/randomization (visit 1) and must agree to use an effective method of birth control throughout the study.\n- Patients with the capacity to provide informed consent."}

Exclusion criteria

• {"criterion_text":"- Any prior history of myocardial infarction, angina, coronary revascularization, coronary stenosis >30%, stroke, transient ischemic attack, or known heart failure\n- Known chronic renal insufficiency defined as an estimated glomerular filtration rate (eGFR), using the MDRD equation, of < 35 mL/min/1.73m2\n- History of cancer or lymphoproliferative disease within the last 3 years other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or low-grade prostate cancer\n- Inflammatory bowel disease (Crohn’s disease or ulcerative colitis) or chronic diarrhea\n- Peptic ulcer diagnosed within the last 24 months or previous gastrointestinal bleeding, except for mild hemorrhoidal bleeding more than 5 years ago which is permitted (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)\n- Pre-existent progressive neuromuscular disease or known CPK level > 3 times the upper limit of normal as measured within the past 30 days and determined to be non-transient through repeat testing\n- Any of the following known parameters as measured within the past 90 days, and determined to be non-transient through repeat testing: a. hemoglobin < 100 g/L b. white blood cell count < 3.0 X 109 /L c. platelet count <110 X 109 /L d. ALT > 3 times the upper limit of normal (ULN) e. total bilirubin > 2 times ULN (unless due to Gilbert syndrome, which is allowed)\n- History of cirrhosis, chronic active hepatitis or severe hepatic disease\n- Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study or for 6 months after the last dose of study medication\n- History of clinically significant drug or alcohol abuse in the last year\n- Patient is currently using or plans to begin chronic systemic steroid therapy (oral or intravenous) during the study (topical or inhaled steroids are allowed, as well as replacement corticosteroids for adrenal insufficiency)\n- Current chronic treatment with aspirin or another antiplatelet agent (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)\n- Chronic treatment with an anticoagulant agent (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)\n- Current use of colchicine for other indications (mainly chronic indications consisting of Familial Mediterranean Fever or gout); there is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrolment\n- History of an allergic reaction or significant sensitivity to colchicine\n- History of an allergic reaction or significant sensitivity to aspirin (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)\n- Chronic treatment with an anti-inflammatory agent (for example, anti-TNF-alpha or nonsteroidal anti-inflammatory drug (NSAID))\n- Use of an investigational chemical agent less than 30 days or 5 half-lives prior to the screening visit (whichever is longer)\n- Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the time from randomization to the first event of the composite of cardiovascular death, resuscitated cardiac arrest, myocardial infarction (non-fatal), stroke (non-fatal), or urgent hospitalization for angina requiring coronary revascularization.","definition_or_measurement_approach":"Time from randomization to first occurrence of the composite cardiovascular endpoint (cardiovascular death, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, or urgent hospitalization for angina requiring coronary revascularization)."}

Secondary endpoints

• {"endpoint_text":"- Times from randomization to each component of the primary endpoint; and to the first event of the composite of cardiovascular death, resuscitated cardiac arrest, myocardial infarction (non-fatal) or stroke (non-fatal)","definition_or_measurement_approach":"Time-to-event analyses from randomization to each individual component and to the first event of the specified composite."}
• {"endpoint_text":"- Total burden of first and subsequent primary endpoint events","definition_or_measurement_approach":"Aggregate count/burden of first and subsequent events related to the primary endpoint during follow-up."}
• {"endpoint_text":"- Change from randomization in MoCA score at yearly follow-ups (excluding the first-year visit) until the end-of-study visit.","definition_or_measurement_approach":"Change in Montreal Cognitive Assessment (MoCA) score measured at annual follow-ups (excluding first-year visit) through end of study."}
• {"endpoint_text":"- Number and proportion of patients experiencing serious adverse events.","definition_or_measurement_approach":"Counts and proportions of participants with serious adverse events as recorded in safety reporting."}
• {"endpoint_text":"- For exploratory and safety end points please refer to the study protocol.","definition_or_measurement_approach":"Exploratory and additional safety endpoints are defined in the study protocol (refer to protocol document)."}

Methods

• Country-specific recruitment materials and arrangements documented (examples include flyers, posters/affiches, patient invitation letters, GP letters, Assurance Maladie letter (France), Biobank letter). (Documents listed: Flyer_FR, K2_Recruitment material_PatientsLetter_FR_*, K2_Recruitment material_Biopank letter, K1_Recruitment arrangements per country).
• Use of site-based recruitment via participating hospitals, clinics and patient organisations (many trial sites and some patient organisations listed as sites).
• Participant information materials and study medication booklets distributed to potential participants (subject information and ICF documents per country).

Greece

Earliest CTIS Part Ii Submission Date

11-03-2025

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

414

Number Of Participants

500

Portugal

Earliest CTIS Part Ii Submission Date

03-01-2025

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

480

Number Of Participants

500

France

Earliest CTIS Part Ii Submission Date

06-03-2025

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

418

Number Of Participants

1500

Italy

Earliest CTIS Part Ii Submission Date

27-02-2025

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

428

Number Of Participants

500

Finland

Earliest CTIS Part Ii Submission Date

18-02-2025

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

435

Number Of Participants

350

Denmark

Earliest CTIS Part Ii Submission Date

06-03-2025

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

418

Number Of Participants

1000

Primary sponsor

Full Name

Montreal Heart Institute

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Canada

Contract research organisations

Name

Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.

Responsibilities

sponsorDuties code: 1 (as listed in CTIS third parties)

Third parties

• {"country":"Denmark","full_name":"GCP-enheden ved Københavns Universitetshospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Health care"}
• {"country":"Greece","full_name":"Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}